Various patents and other publications are referred to throughout the specification. Each of these publications is incorporated by reference herein, in its entirety.
Neurological diseases and other disorders of the central and peripheral nervous system are among the most debilitating that can be suffered by an individual, not only because of their physical effects, but also because of their permanence. One of such diseases is amyotrophic lateral sclerosis (ALS) (also known as Lou Gehrig's disease).
ALS is a progressive neurodegenerative disease that mainly affects motor neurons resulting in muscle weakness and atrophy. The disease is characterized by selective, premature degeneration and death of motor neurons. Affected neurons show loss of dendrites, cytoskeletal changes and accumulation of proteins and inclusion bodies. ALS results in a progressive paralysis that is typically fatal within a handful of years due to respiratory failure resulting from paralysis of the respiratory muscles. The average duration of disease from onset to death is three to five years. Only about 10% of ALS patients survive for ten or more years. As many as 20,000 to 30,000 people in the United States suffer from ALS and an additional 5,000 are diagnosed each year.
The pathogenic mechanisms of ALS are not fully understood but a variety of processes are thought to contribute to ALS including mitochondrial dysfunction, oxidative stress, excitotoxicity as well as alterations in the cytoskeleton, in axonal transport, protein processing, and calcium homeostasis (Ilieva et al. (2009), J. Cell Biol. 187:761-72). Despite intense effort, very limited therapeutic options have emerged for the slowing disease course, although advances have been made in palliative therapy. Allogeneic cell therapy may provide an effective multi-factorial therapy for the treatment of ALS by elaborating trophic factors, which diminish motor neuron degeneration, preserve motor neuron function and extend life.
Given the debilitating effects of ALS and the lack of treatment, there exists a great need for treating ALS in a patient and thereby improving the patient's quality of life.